The candidate, Dr. Laine Murphey, is a board certified internist and a pharmacologist experienced in studies of cardiovascular physiology. He seeks to continue to progress to independence as a patient-oriented researcher in the field of hypertension through a mentored career development plan that includes bedside research, laboratory studies and a focused curriculum in biostatistics, genetics and study design. The program will take place at Vanderbilt University, which has an historic and strong commitment to the mentored training of clinical researchers. The General Clinical Research Center at Vanderbilt provides the ideal environment for the proposed human studies. Research: Bradykinin, a cardioprotective peptide hormone, is a vasodilator and a natriuretic. In humans, bradykinin contributes to the acute hemodynamic effects of ACE inhibitors, a widely used class of drugs. Studies suggest that endogenous bradykinin may be decreased in human hypertension and that it is modulated by salt-status, ethnic and genetic factors. To date, human studies of systemic bradykinin have been confounded by difficulties in measuring this rapidly metabolized peptide. Prior assays have relied on non-specific radioimmunoassay techniques. Recently, we studied the human in vivo metabolism of systemic bradykinin and identified BK1 -5 as the major stable plasma metabolite of bradykinin. To accurately measure bradykinin and BK1-5, we have developed highly specific and sensitive liquid chromatography-mass spectroscopy assays for these two peptides. Together, these advances in the field now provide powerful methods to determine the role of systemic bradykinin in cardiovascular homeostasis. In this application, I propose to use these new tools to test directly the hypothesis that systemic bradykinin is decreased in hypertension and that it is modulated by genetic, ethnic and environmental factors. The implementation of these studies in a mentored environment, together with participation in directed course work, will provide the applicant with the tools to become an independent patient-oriented researcher.